EP0003897A1 - Phosphinegold(I)salts, process for their preparation and compositions containing them - Google Patents

Phosphinegold(I)salts, process for their preparation and compositions containing them Download PDF

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Publication number
EP0003897A1
EP0003897A1 EP79300245A EP79300245A EP0003897A1 EP 0003897 A1 EP0003897 A1 EP 0003897A1 EP 79300245 A EP79300245 A EP 79300245A EP 79300245 A EP79300245 A EP 79300245A EP 0003897 A1 EP0003897 A1 EP 0003897A1
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Prior art keywords
phosphine
gold
phenyl
pyridine
perchlorate
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German (de)
French (fr)
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EP0003897B1 (en
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David Taylor Hill
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SmithKline Beecham Corp
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SmithKline Beecham Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/58—Pyridine rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • This invention relates to phosphinegold(I) salts having antiarthritic activity. In particular, they are of use in the treatment of rheumatoid arthritis. This invention also relates to processes for preparing these compounds and to compositions containing them.
  • R 1 is (C 1-4 ) alkyl, (C 1-4 ) alkoxy or phenyl, said phenyl being optionally substituted by halogen or (C 1-4 ) alkoxy;
  • R2 and R31 which are the same or different, are (C 1-4 ) alkyl or (C 1-4 ) alkoxy; and
  • X is a weakly nucleophilic anion.
  • a particular compound of this invention is represented by formula I in which R 1 , R 2 and R 3 are all ethyl.
  • the anion X in formula I is weakly nucleophilic, for example perchlorate (ClO 4 - ), iodate (IO 4 - ), tetrafluoroborate (BF 4 - ) or hexafluorophosphate (PF 6 - ).
  • the compounds of this invention can be prepared by the following procedure: where R 1 , R 2 , R 3 and X are as defined above and X' is halo.
  • a halo(trisubstituted phosphine)gold(I) compound is reacted with a silver salt AgX and pyridine to give a compound of formula I.
  • the reaction is conveniently carried out in a solvent, for example acetone, at room temperature.
  • halo(trisubstituted phosphine)gold(I) starting materials in the above procedure can be prepared by reacting thiodiglycol with a gold acid halide trihydrate to give halo[di[2-hydroxyethyl)-sulfide]gold(I) which is then reacted with a trisubstituted phosphine.
  • the compounds of formula I can be used in the treatment of arthritis. This activity is demonstrated by the following test procedure.
  • Inhibition of adjuvant-induced polyarthritis in rats is produced by compounds of formula I at daily oral doses of about 20 mg./kg. (calculated on gold content).
  • adjuvant arthritis in rats is produced by a single intradermal injection of 0.75 mg. of Mycobacterium butyricum suspended in white paraffin oil into the left hindpaw footpad.
  • the injected paw becomes inflamed (increased volume) and reaches maximal size within three to five days (primary lesion).
  • the animals exhibit a decrease in body weight gain during the initial period.
  • the adjuvant arthritis occurs after approximately ten days, and it is characterized by inflammation of the non-injected right hind leg, decrease in body weight, and further increase in the volume of the injected left hind leg.
  • Compounds to be tested are administered daily, beginning on the day of the adjuvant injection, and for 17 days thereafter, exclusive of days 4, 5, 11 and 12.
  • Antiarthritic activity is shown by the ability of the tested compounds to inhibit the development of either primary or second lesions of adjuvant arthritis.
  • the compounds of formula I are preferably administered in conventional dosage forms prepared by combining a compound of formula I with a standard pharmaceutical carrier according to conventional procedures. These procedures can involve mixing, granulating and compressing or dissolving the ingredients as appropriate to the desired preparation.
  • the invention therefore provides pharmaceutical compositions comprising a compound of formula I and a pharmaceutically acceptable carrier, preferably in dosage unit form. Oral dosage forms are preferred.
  • the pharmaceutical carrier employed can solid or liquid.
  • solid carriers are lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, stearic acid and the like.
  • liquid carriers are syrup, peanut oil, olive oil, water and the like.
  • the carrier can include a time delay material well known to the art, for example glyceryl monostearate or glycaryl distearate, alone or with a wax.
  • compositions can be tableted, be placed in a hard gelatin capsule in powder or pellet form, or be in the form of a troche or lozenge.
  • the amount of solid carrier can be varied widely but preferably will be from about 25 mg. to about 1 g. per dosage unit.
  • a liquid carrier is used, the compositions can be in the form of a syrup, an emulsion, a soft gelatin capsule, a sterile injectable liquid for example in an ampoule, or a non-aqueous liquid suspension.
  • each dosage unit will contain a compound of formula I in an amount of from about 1 mg. to about 10 mg.
  • the compounds of formula I will be administered in an amount sufficient to produce antiarthritic activity.
  • the route of administration can be oral or parenteral, preferably oral.
  • doses will be administered 1 or 2 times a day, with the daily dosage regimen being preferably from about 1 mg. to about 12 mg.
  • the product is (pyridine)-(triethylphosphine)gold(I) tetrafluoroborate.
  • the product is (pyridine)(triethylphosphine)gold(I) hexafluorophosphate.
  • the product is (pyridine)[(p-chlorophenyl)(diethyl)phosphine]gold(I) iodate.
  • the product is (pyridine)[(p-ethoxyphenyl)-(diethyl)phosphine]gold(I) perchlorate.
  • the above ingredients are screened, mixed and filled into a hard gelatin capsule.
  • the capsules are administered orally to subjects in need of antiarthritic treatment in amounts within the daily dose range given hereabove.
  • compositions for example tablets, containing a compound of formula I as the active ingredient are formulated by standard procedures.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)

Abstract

(Pyridine) (trisubstituted phosphine) gold (I) salts. These compounds have antiarthritic activity. They can be prepared by reacting a halo (trisubstituted phosphine) gold (I) compound with a silver salt and pyridine.

Description

  • This invention relates to phosphinegold(I) salts having antiarthritic activity. In particular, they are of use in the treatment of rheumatoid arthritis. This invention also relates to processes for preparing these compounds and to compositions containing them.
  • According to the present invention there are provided compounds of the formula:
    Figure imgb0001
    where R1 is (C1-4) alkyl, (C1-4) alkoxy or phenyl, said phenyl being optionally substituted by halogen or (C1-4) alkoxy; R2 and R31 which are the same or different, are (C1-4) alkyl or (C1-4) alkoxy; and X is a weakly nucleophilic anion.
  • A particular compound of this invention is represented by formula I in which R1, R2 and R3 are all ethyl.
  • The anion X in formula I is weakly nucleophilic, for example perchlorate (ClO4 -), iodate (IO4 -), tetrafluoroborate (BF4 -) or hexafluorophosphate (PF6 -).
  • The compounds of this invention can be prepared by the following procedure:
    Figure imgb0002
    where R1, R2, R3 and X are as defined above and X' is halo.
  • According to the above procedure, a halo(trisubstituted phosphine)gold(I) compound is reacted with a silver salt AgX and pyridine to give a compound of formula I. The reaction is conveniently carried out in a solvent, for example acetone, at room temperature.
  • The halo(trisubstituted phosphine)gold(I) starting materials in the above procedure can be prepared by reacting thiodiglycol with a gold acid halide trihydrate to give halo[di[2-hydroxyethyl)-sulfide]gold(I) which is then reacted with a trisubstituted phosphine.
  • The compounds of formula I can be used in the treatment of arthritis. This activity is demonstrated by the following test procedure.
  • Inhibition of adjuvant-induced polyarthritis in rats, as measured by reduction of rat paw edema, is produced by compounds of formula I at daily oral doses of about 20 mg./kg. (calculated on gold content). In this test procedure, adjuvant arthritis in rats is produced by a single intradermal injection of 0.75 mg. of Mycobacterium butyricum suspended in white paraffin oil into the left hindpaw footpad. The injected paw becomes inflamed (increased volume) and reaches maximal size within three to five days (primary lesion). The animals exhibit a decrease in body weight gain during the initial period. The adjuvant arthritis (second lesion) occurs after approximately ten days, and it is characterized by inflammation of the non-injected right hind leg, decrease in body weight, and further increase in the volume of the injected left hind leg. Compounds to be tested are administered daily, beginning on the day of the adjuvant injection, and for 17 days thereafter, exclusive of days 4, 5, 11 and 12. Antiarthritic activity is shown by the ability of the tested compounds to inhibit the development of either primary or second lesions of adjuvant arthritis.
  • In therapy, the compounds of formula I are preferably administered in conventional dosage forms prepared by combining a compound of formula I with a standard pharmaceutical carrier according to conventional procedures. These procedures can involve mixing, granulating and compressing or dissolving the ingredients as appropriate to the desired preparation. The invention therefore provides pharmaceutical compositions comprising a compound of formula I and a pharmaceutically acceptable carrier, preferably in dosage unit form. Oral dosage forms are preferred.
  • The pharmaceutical carrier employed can solid or liquid. Examples of solid carriers are lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, stearic acid and the like. Examples of liquid carriers are syrup, peanut oil, olive oil, water and the like. Similarly, the carrier can include a time delay material well known to the art, for example glyceryl monostearate or glycaryl distearate, alone or with a wax.
  • A wide variety of pharmaceutical forms can be employed. Thus, if a solid carrier is used, the compositions can be tableted, be placed in a hard gelatin capsule in powder or pellet form, or be in the form of a troche or lozenge. The amount of solid carrier can be varied widely but preferably will be from about 25 mg. to about 1 g. per dosage unit. If a liquid carrier is used, the compositions can be in the form of a syrup, an emulsion, a soft gelatin capsule, a sterile injectable liquid for example in an ampoule, or a non-aqueous liquid suspension.
  • Preferably, each dosage unit will contain a compound of formula I in an amount of from about 1 mg. to about 10 mg.
  • In therapy, the compounds of formula I will be administered in an amount sufficient to produce antiarthritic activity. The route of administration can be oral or parenteral, preferably oral. Advantageously, doses will be administered 1 or 2 times a day, with the daily dosage regimen being preferably from about 1 mg. to about 12 mg.
  • In determining the amount of a compound of formula I to be used in therapy, the activity of the compound as well as the size of the animal being treated must be considered.
  • The following Examples are given by way of illustration only.
    • EXAMPLE 1
  • A solution of 2.07 g. (0.01 mole) of silver perchlorate in 30 ml. of acetone was added dropwise to a solution of 3.5 g. (0.01 mole) of chloro-(triethylphosphine)gold(I) and 0.8 ml. of pyridine in 50 ml. of acetone. After stirring 30 minutes, the mixture was filtered, and the solvent was removed at reduced pressure to give a solid product. Recrystallization of this solid product from acetone upon the addition of ether to the cloud point and cooling to -78°C. gave (pyridine)(triethylphosphine)gold(I) perchlorate, m.p. 71-73 C.
    • EXAMPLE 2
  • In the procedure of Example 1 using, in place of chloro(triethylphosphine)gold(I), the following:
    • chloro(trimethylphosphine)gold(I)
    • chloro(triisopropylphosphine)gold(I)
    • chloro(tributylphosphine)gold(I)
    the products are:
    • (pyridine)(trimethylphosphine)gold(I) perchlorate
    • (pyridine)(triisoprdpylphosphine)gold(I) perchlorate
    • (pyridine)(tributylphosphine)gold(I) perchlorate. EXAMPLE 3
  • Using silver iodate in the procedure of Example 1 in place of silver perchlorate gives (pyridine)(triethylphosphine)gold(I) iodate.
  • Similarly, using silver tetrafluoroborate in place of silver perchlorate, the product is (pyridine)-(triethylphosphine)gold(I) tetrafluoroborate.
  • Also, using silver hexafluorophosphate, the product is (pyridine)(triethylphosphine)gold(I) hexafluorophosphate.
    • EXAMPLE 4
  • A solution of 14 g. (0.11 mole) of thiodiglycol in 35 ml. of ethanol was added to a solution of 22.1 g. (0.055 mole) of gold acid chloride trihydrate in 105 ml. of distilled water at O°C. A solution of 10 g. of (diethyl)(phenyl)-phosphine in 35 ml. of ethanol was then added dropwise. After stirring for 30 minutes, the mixture was extracted with chloroform, and the chloroform extracts were dried and filtered, and the solvent was removed in vacuo to give an oil. Purification of this oil by dry column chromatography and recrystallization from ether gave chloro[(diethyl)(phenyl)phosphine]gold(I) as white cyrstalline material having a melting point of 61-63°C.
  • Using chloro[(diethyl)(phenyl)phosphine]-gold(I) in place of chloro(triethylphosphine)gold(I) in the procedure of Example 1 gives (pyridine)-[(diethyl)(phenyl)phosphine]gold(I) perchlorate.
    • EXAMPLE 5
  • Using, in place of (diethyl)(phenyl)-phosphine, in the procedure of Example 4, the following phosphines:
    • (dimethyl)(phenyl)phosphine
    • (dipropyl)(phenyl)phosphine
    • (dibutyl)(phenyl)phosphine
    • (diisobutyl)(phenyl)phosphine
    • (ethyl)(methyl)(phenyl)phosphine
    • (methyl) (propyl) (phenyl) phosphine
    • (t-butyl)(methyl)(phenyl)phosphine
    the products are:
    • (pyridine)[(dimethyl)(phenyl)phosphine]-gold(I) perchlorate
    • (pyridine) [(dipropyl) (phenyl)phosphine]-gold(I) perchlorate
    • (pyridine) [ (dibutyl) (phenyl) phosphine] - gold(I) perchlorate
    • (pyridine)[(diisobutyl)(phenyl)phosphine]-gold(I) perchlorate
    • (pyridine)[(ethyl)(methyl)(phenyl)phosphine]-gold(I) perchlorate
    • (pyridine) [(methyl) (propyl) (phenyl)phosphine]-gold(I) perchlorate
    • (pyridine) [(t-butyl) (methyl) (phenyl)phosphine]-gold(I) perchlorate.
    EXAMPLE 6
  • A solution of 13.4 g. (0.11 mole) of thiodiglycol in 30 ml. of ethanol was mixed with a solution of 20.0 g. (0.05 mole) of gold acid chloride trihydrate in 90 ml. of distilled water. When the solution was almost colorless, it was cooled to O°C. and 10 g. (0.05 mole) of (diethoxy)(phenyl)phosphine in 30 ml. of ethanol was added dropwise to the stirred solution. After stirring for one hour, the two phase reaction mixture was extracted with chloroform, and the chloroform extract was washed with water, dried over magnesium sulfate and filtered. The solvent was removed from the filtrate at reduced pressure to give an oil. Chromatography ('Florisil'/chloroform) gave chloro[(diethoxy)-(phenyl)phosphine]gold(I) as a colorless oil in the first fraction.
  • Using chloro](diethoxy)(phenyl)phosphine]-gold(I) in place of chloro(triethylphosphine)gold(I) in the procedure of Example 1 gives (pyridine)[(diethoxy)-(phenyl)phosphine]gold(I) perchlorate.
    • EXAMPLE 7
  • Using (dimethoxy) (phenyl) phosphine in place of (diethoxy)(phenyl)phosphine in the procedure of Example 6 gives, as the product, (pyridine) [(dimethoxy)-(phenyl)phosphine]gold(I) perchlorate.
  • Similarly, using (p-chlorophenyl) (diethoxy)-phosphine and (p-bromophenyl)(diethoxy)phosphine, the products are (pyridine) [(p-chlorophenyl) (diethoxy)-phosphine] gold (I) perchlorate and (pyridine) [(p-bromophenyl) (diethoxy)phosphine]gold(I) perchlorate.
  • Also, using (diethoxy) (p-methoxyphenyl)-phosphine in the procedure of Example 6, the product is (pyridine) [(diethoxy) (p-methoxyphenyl)-phosphine]gold(I) perchlorate.
  • In the same manner, using (phenyl) (dipropoxy)-phosphine and (dibutoxy) (phenyl) phosphine, the products are (pyridine) [ (phenyl) (dipropoxy) phosphine] gold (I) perchlorate and (pyridine) [(dibutoxy) (phenyl)phosphine]-gold(I) perchlorate.
    • EXAMPLE 8
  • A solution of 10 g. (0.08 mole) of diethylphosphinous chloride in 100 ml. of ether was added to a solution of p-chlorophenyllithium [prepared from 15.4 g. (0.08 mole) of p-chlorobromobenzene in 100 ml. of ether and 54 ml. of 1.5M n-butyllithium in hexane] under a nitrogen atmosphere. After 30 minutes, the reaction mixture was quenched with a few drops of ethyl acetate, and the solvent was removed at reduced pressure. Distillation of the residual oil gave (p-chlorophenyl)(diethyl)phosphine, b.p. 86-89°C. at 1.5 mm.
  • A solution of 4.7 g. (0.038 mole) of thiodiglycol in 30 ml. of ethanol was added to a solution of 7.7 g. (0.019 mole) of gold acid chloride trihydrate in 45 ml. of distilled water. The colorless solution was cooled to 0°C., and a solution of 3.9 g. (0.019 mole) of (p-chlorophenyl)(diethyl)phosphine in 15 ml. of ethanol was added. After stirring for 45 minutes, the layers were separated, and methylene chloride was added to the organic phase. The resulting solution was washed with distilled water, then dried with sodium sulfate and filtered, and the solvent was removed in vacuo to give an oily residue. This material was dissolved in ether and an equal volume of low boiling petroleum ether was added. The solid precipitate was filtered off and air dried to give chloro[(p-chlorophenyl)(diethyl)phosphine]gold(I), m.p. 77-790C.
  • By the procedure of Example 1, using chloro[p-chlorophenyl)(diethyl)phosphine]gold(I), the product is (pyridine)[(p-chlorophenyl)(diethyl)phosphine]-gold(I) perchlorate.
  • Using silver iodate in place of silver perchlorate, the product is (pyridine)[(p-chlorophenyl)(diethyl)phosphine]gold(I) iodate.
    • EXAMPLE 9
  • A solution of 10 g. (0.08 mole) of diethylphosphinous chloride in 100 ml. of ether was added to a solution of p-methoxyphenyllithium [prepared from 23.4 g. (0.1 mole) of p-iodoanisole in 100 ml. of ether and 62.5 ml. of 1.6 M n-butyllithium in hexane] under a nitrogen atmosphere. After 40 minutes, the reaction mixture was filtered, and the solvent was removed at reduced pressure. Distillation of the residual oil gave (diethyl)(p-methoxyphenyl)phosphine as a colorless liquid, b.p. 85-90°C. at 0.5 mm.
  • A solution of 6.8 g. of thiodiglycol in 40 ml. of ethanol was added to a solution of 11.1 g. of gold acid chloride trihydrate in 60 ml. of distilled water. When the solution became colorless, it was cooled to 0°C., and a solution of 5.5 g. of (diethyl)(p-methoxyphenyl)phosphine in 15 ml. of ethanol was added. After stirring 20 minutes, the reaction mixture was extracted with methylene chloride. The combined methylene chloride extracts were washed with water, dried with sodium sulfate and filtered, and the solvent was removed at reduced pressure to give a pale gold oil. Purification was accomplished with dry column chromatography (alumina/chloroform) to give chloro-[(diethyl)(p-methoxyphenyl)phosphine]gold(I) as a colorless oil.
  • Using chloro [(diethyl)(p-methoxyphenyl)-phosphine]gold(I) in the procedure of Example 1, the product is (pyridine)[(diethyl)(p-methoxyphenyl)-phosphine]gold(I) perchlorate.
    • EXAMPLE 10
  • Using the following tri-substituted phosphines in place of (diethoxy)(phenyl)phosphine in the procedure of Example 6:
    • (ethoxy)(methyl)(phenyl)phosphine
    • (ethoxy)(ethyl)(phenyl)phosphine
    • (butoxy) (ethoxy) (phenyl)phosphine
    • (p-chlorophenyl)(ethoxy)(ethyl)phosphine
    the following products are obtained, respectively:
    • (pyridine)[(ethoxy)(methyl)(phenyl)phosphine]-gold(I) perchlorate
    • (pyridine)[(ethoxy)(ethyl)(phenyl)phosphine]-gold(I) perchlorate
    • (pyridine)[(butoxy)(ethoxy)(phenyl)phosphine]-gold(I) perchlorate
    • (pyridine)[(p-chlorophenyl)(ethoxy)(ethyl)-phosphine]gold(I) perchlorate.
    EXAMPLE 11
  • Using, in the procedure of Example 4, (p-bromophenyl)(diethyl)phosphine in place of (diethyl)-(phenyl)phosphine, the product is (pyridine)[(p-bromophenyl) (diethyl)phosphine]gold(I) perchlorate.
  • Similarly, using (p-ethoxyphenyl)(diethyl)-phosphine, the product is (pyridine)[(p-ethoxyphenyl)-(diethyl)phosphine]gold(I) perchlorate.
    • EXAMPLE 12
  • Figure imgb0003
  • The above ingredients are screened, mixed and filled into a hard gelatin capsule.
  • The capsules are administered orally to subjects in need of antiarthritic treatment in amounts within the daily dose range given hereabove.
  • Similarly, the other gold compounds of formula I can be formulated into capsules by the procedure of Example 12.
  • Other pharmaceutical compositions, for example tablets, containing a compound of formula I as the active ingredient are formulated by standard procedures.

Claims (9)

1. A compound of the formula:
Figure imgb0004
where R1 is (C1-4) alkyl, (C1-4) alkoxy or phenyl, said phenyl being optionally substituted by halogen or (C1-4) alkoxy; R2 and R3, which are the same or different, are (C1-4) alkyl or (C1-4) alkoxy; and X is a weakly nucleophilic anion.
2. A compound according to Claim 1, wherein X is perchlorate, iodate, tetrafluoroborate or hexafluorophosphate.
3. A compound according to Claim 1, wherein R 1, R2 and R3 are all ethyl.
4. (Pyridine)(triethylphosphine)gold(I) perchlorate.
5. A pharmaceutical composition characterized in that it comprises a pharmaceutical carrier and a compound as claimed in any one of Claims 1 to 4.
6. A pharmaceutical composition according to Claim 5, characterized in that it is in dosage unit form.
7. A process for preparing a compound according to Claim 1, characterized in that a compound of the formula:
Figure imgb0005
 (where R1, R2 and R3 are as defined in Claim 1 and X' is halo) is reacted with a silver salt of the formula:
AgX
(where X is as defined in Claim 1) and pyridine,
8. A process according to Claim 7, characterized in that a silver salt AgX is used where X is perchlorate, iodate, tetrafluoroborate or hexafluorophosphate.
9. A process according to Claim 7, characterized in that a compound of formula II is used where R1, R2 and.R3 are all ethyl.
EP79300245A 1978-02-21 1979-02-19 Phosphinegold(i)salts, process for their preparation and compositions containing them Expired EP0003897B1 (en)

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Application Number Priority Date Filing Date Title
US879319 1978-02-21
US05/879,319 US4171360A (en) 1978-02-21 1978-02-21 Phosphinegold (I) salts having antiarthritic activity

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EP0003897A1 true EP0003897A1 (en) 1979-09-05
EP0003897B1 EP0003897B1 (en) 1983-05-25

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4921847A (en) * 1988-05-23 1990-05-01 Engelhard Corporation Trihalo(amine)gold(III) anti-tumor complexes
US6069253A (en) * 1998-12-09 2000-05-30 Council Of Scientific And Industrial Research Process for the preparation of new transition metal complexes
US6294687B1 (en) * 1999-01-09 2001-09-25 Council Of Scientific And Industrial Research Process for the preparation of saturated carboxylic acids and their esters
US6084117A (en) * 1999-11-22 2000-07-04 Albemarle Corporation Production of silated haloarenes by selective silylation of polyhaloarenes

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2081345A1 (en) * 1969-12-12 1971-12-03 Smith Kline French Lab
US3842107A (en) * 1973-07-23 1974-10-15 Smithkline Corp Phosphine or phosphite gold complexes of thiobenzoic acid and substituted thiophenols

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2081345A1 (en) * 1969-12-12 1971-12-03 Smith Kline French Lab
US3842107A (en) * 1973-07-23 1974-10-15 Smithkline Corp Phosphine or phosphite gold complexes of thiobenzoic acid and substituted thiophenols

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JOURNAL OF THE CHEMICAL SOCIETY DALTON TRANSACTIONS, (15), pages 1434-9 (1977) * Page 1438, table 5; page 1439, experimental * *

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US4171360A (en) 1979-10-16
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EP0003897B1 (en) 1983-05-25

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